This R21 proposal builds upon the observations made in the RO1 (A1032947-11) which indicates that the expression of TROSPA, a tick receptor for OspA, is up regulated upon infection by Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme disease. This presumably facilitates Borrelia colonization of the tick midgut. B. burgdorferi likely modulates the tick transcriptome to ensure its survival and transmission. [unreadable] [unreadable] This aspect of Lyme disease has not been investigated and could open novel venues to vector and disease control. The proposed project aims to broaden the scope of the RO1 and shift the focus beyond TROSPA and OspA. Using cDNA arrays the global changes that occur in the tick salivary gland transcriptome during the infection and transmission of B. burgdorferi will be defined. The functional significance of these gene products in enabling B. burgdorferi invasion of tick salivary glands and its subsequent transmission will be evaluated by specifically silencing the selected tick genes in vivo, using the RNA interference technology. The results of this project will provide insights into tick-Borrelia interactions and enable identification of novel tick -based targets for blocking transmission of Lyme disease. This study will also serve to develop the infrastructure and genetic tools essential for making rapid progress in the field of tick functional genomics. This investigation may therefore serve to pave the way for elucidation of mechanisms underlying transmission of other tick-borne pathogens. [unreadable] [unreadable]